Finite-Element Stress Analysis of a Multicomponent Model of Sheared and Focally-Adhered Endothelial Cells |
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Authors: | Michael C Ferko Amit Bhatnagar Mariana B Garcia Peter J Butler |
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Institution: | (1) Department of Bioengineering, The Pennsylvania State University, 205 Hallowell Building, University Park, PA 16802, USA;(2) Department of Bioengineering, The Pennsylvania State University, 228 Hallowell Building, University Park, PA 16802, USA |
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Abstract: | Hemodynamic forces applied at the apical surface of vascular endothelial cells may be redistributed to and amplified at remote
intracellular organelles and protein complexes where they are transduced to biochemical signals. In this study we sought to
quantify the effects of cellular material inhomogeneities and discrete attachment points on intracellular stresses resulting
from physiological fluid flow. Steady-state shear- and magnetic bead-induced stress, strain, and displacement distributions
were determined from finite-element stress analysis of a cell-specific, multicomponent elastic continuum model developed from
multimodal fluorescence images of confluent endothelial cell (EC) monolayers and their nuclei. Focal adhesion locations and
areas were determined from quantitative total internal reflection fluorescence microscopy and verified using green fluorescence
protein–focal adhesion kinase (GFP–FAK). The model predicts that shear stress induces small heterogeneous deformations of
the endothelial cell cytoplasm on the order of <100 nm. However, strain and stress were amplified 10–100-fold over apical
values in and around the high-modulus nucleus and near focal adhesions (FAs) and stress distributions depended on flow direction.
The presence of a 0.4 μm glycocalyx was predicted to increase intracellular stresses by ∼2-fold. The model of magnetic bead
twisting rheometry also predicted heterogeneous stress, strain, and displacement fields resulting from material heterogeneities
and FAs. Thus, large differences in moduli between the nucleus and cytoplasm and the juxtaposition of constrained regions
(e.g. FAs) and unattached regions provide two mechanisms of stress amplification in sheared endothelial cells. Such phenomena
may play a role in subcellular localization of early mechanotransduction events. |
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Keywords: | Cell mechanics Endothelial cells Total internal reflection Focal adhesions Mechanotransduction Continuum Elastic Glycocalyx Focal adhesion kinase |
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